Triazole derivatives



'phenylethyl, phenylpropyl, etc.)

Patented Apr. '24, 1945 UNTED STATES PATENT OFFlCE TRIAZOLE DERIVATIVES Gaetano F. DAlelio, Pittsfield, Mass.,'assignor to General Electric Company, a corporation of New York 1 No Drawing. Application December 26, 1942,

Serial No. 470,220

14 Claims.

This invention relates to new chemical compounds and more particularly to triazole derivatives. The invention especially is concerned with the production of new and useful acylaminoarylamino triazoles.

The triazole derivatives of this invention may be represented by the following general formula:

where R represents a member of the class consisting of hydrogen and monovalent hydrocarbon radicals, R represents a monovalent hydrocarbon radical, and Z represents a member of the class consisting of divalent aromatic and nuclearly 'substituted, more particularly nuclearly halogenated, aromatic hydrocarbon radicals.

Illustrative examples of monov alent hydrocarbon radicals that R and R in the above formula may represent are: aliphatic (e. g., methyl, ethyl, propyl, isopropyl, butyl, secondary butyl, isobutyl, butenyl, amyl, isoamyl, hexyl, octyl, allyl, methallyl, crotyl, etc), including cycloaliphatic (e. g" cyclopentyl, cyclopentenyl, cyelohexyl, cyclohexenyl, cycloheptyl, etc.); aryl (e. g., phenyl, diphenyl or xenyl, naphthyl, anthracyl, etc); aliphatic-substituted aryl (e. g., tolyl, xylyl, ethylphenyl, propylphenyl, isopropylphenyl, allylphenyl, z-butenylphenyl, propenylphenyl, tertiarybutylphenyl, methylnaphthyl, etc.); and arylsubstituted aliphatic (e. g.', benzyl, cinnamyl, Preferably R represents hydrogen, in which case the compounds correspond to the following general where Z and R have the same meaning as given above with reference to Formula I. However, there also may be produced in accordance with the present invention chemical compounds corresponding to the following general formulas: III N-NR where R, R and Z have the same meanings as given above with reference to Formula I.

I Illustrative examples of divalent radicals that Z in the above formulas may represent are: di- 5 valent aromatic, e. g., phenylene, xenylene, naphthylene, etc.; divalent aliphatic-substituted aromatic, e. g., 2,4-tolylene, ethyl 2,5-phenylene, isopropyl 3,4-phenylene, l-butyl 2.,4-naphthylene,

1,4-dimethyl 2,3-phenylene, etc.; radicals that may be classed either as divalent aliphatic-substituted aromatic or as divalent aromatic-substituted aliphatic and wherein the-free bond of the aromatic nucleus is attached to the acylamino radical, e. g., 4,alpha-tolylene, 3,beta-phenyleneethyl, 4,alpha-xylylene, 2,gamma-phenylenebutyl,

etc. and their homologues, as well as those .di-

valent radicals with one 'or -more of their nuclear hydrogen atoms replaced by a substituerit, e. en, acyl, allgvl, alkenyl, hydroxy, alkoxy, aryloxy, o carboalkoxy, carboaroxy, sulfamyl, an acylamino emit-r) grouping in addition to the single acylamino grouping shown, for example, in Formula I, etc.'

Specific examples of substituted divalent radicals that Z may represent are chlorophenylene, bromophenylene, chloroxenylene, chloronaphthylene, chlorotolylene, bromotolylene, ethoxyphenylene, actophenylene, actoxyphenylene, aminophenylene, carboethoxyphenylene, sulfamylphenylene, carbophenoxyphenylene, hydroxyphenylene', phenoxyphenylene, methylphenylene (tolylene), allylphenylene, etc. Preferably Z is phenylene or tolylene.

The new compounds of this invention may be used, for example, as pharmaceuticals, insecticides, fungicides, plasticizers and as intermediates 4 in the preparation of derivatives thereof, e. g., 40 ureido, acyl, hydrazino, carbamyl, amidine,

methylol, methylene, etc., derivatives of themdividual compound embraced by Formula I, These new compounds are especially valuable in the preparation of synthetic resinous ;compositions..

the chemical compounds of this invention. I prefer to prepare them by effecting reaction under heat between a hydrazine corresponding to the general formula Or, when the reaction is carried out in the presence of an acid effective in binding the ammonia liberated during the reaction, it may be represented by the following general equation:

In Equations VII and VIII, R, R and Z have the same meanings as given above with reference to Formula I, and HA (Equation VIII) represents an acid, which may be either organic or inorganic but which preferably is inorganic. Illustrative examples of organic and inorganic acids that may be used to bind the ammonia in the form of a salt are oxalic, acetic, hydrochloric, hydrobromic, sulfuric, etc. -The reaction advantageously is carried out in an aqueous solution containing an inorganic acid. However, other solvents or mixtures of solvents may be used, e. g.,"a1c0h01s, ethers, dioxane, benzene, etc. The reaction may be carried out under a variety of temperature and pressure 'conditions. Ordinarily the reaction is eflected at atmospheric pressure under reflux at the boiling temperature of the reaction mess.

The acid represented by HA in Equation VIII may constitute one of the starting materials, togather with the hydrazine and the acylaminoaryl biguanide. Or, if desired, the acid may be introduced into the reaction mixture in other forms. For example, a Part of the acid may be employed in a free or solution state and a. part in the form of a mono salt of the acylaminoaryl biguanide or of the hydrazine; or, a part of the acid may be used in the form of a mono salt of the hydrazine and a part in the form of a mono salt of the acylaminoarylbiguanide.

Illustrative examples of hydrazines that may be used, depending upon the particular endproduct desired, are: V I Hydrazine (or hydrazine hydrate) Methyl hydrazine Ethyl hydrazine Propyl hydrazine Isobutyl hydrazine Phenyl hydrazine Allyl hydrazine Propenyl hydrazine Cyclohexyl hydrazine Tolyl hydrazines Xylyl, hydrazines Phenethyl hydrazine Ethylphenyl hydrazines Octyl hydrazine Naphthyl hydrazines Illustrative examples of acylaminoaryl biguanide that may be employed, depending upon the particular end-product desired, are:

Acetylaminophenyl biguanides (acetamidophenyl biguanides), including ortho-(acetylamino) phenyl biguanide, meta-(acetylamino) phenyl biguanide and para-jacetylamino) phenyl biguanide *Acetylaminotolyl biguanides, which may be represented by the formula Acetylaminoxylyl biguanides Acetylaminonaphthyl biguanides Acetylaminoxenyl biguanides, which may be represented by the formula or by the formula 0 XI- 7 (Q il I|-IH I|\|IH NH- -cH, H,N-d-NH-c-Nn- Propanoylaminophenyl biguanides Butanoylaminophenyl biguanides Bu'tanoylaminotolyl biguanides- Isobutanoylaminoxylyl biguanides Propenoylaminophenyl biguanides Propenoylaminonaphthyl biguanides Cyclopentanoylaminophenyl biguanides Benzoylaminophenyl biguanides Acetylamino-(chloro)--phenyl biguanides, which may be represented by the formula.

XIII

Toiuylaminoxenyl biguan'ides, which may be represented by the formula or by the formula (N-methyl acetylaminophenyl) biguanides (N-ethyl propanoylainino ethylphenyl) guanides (N-isobu'tyl benzoylamino methylnaphthyl) biguanide p (N-cyclopentyl benzoylamino phenyl) bizu'anides' (N-phenvl methylcyclopentanoylamino chlorophenyl) biguanides, which may be represented by the formula (N-xenyl acetylamino bromotolyl) biguanides,

which may be represented by the formula j xvi II f? Ethylbenzoylaminophenyl biguanides. V

The acylaminoaryl'biguanides used in practicing the present invention are prepared, for example, by eflecting reaction between biguanide or dicyandlamide -(cyanoguanidine) and an acylaminoaryl amine, preferably in the presence of an inorganic acid.

(Para-acetamido phenyl) biguanide hydrochloride I 135.2 Hydrazine hydrate (in 34.5 parts water)-.. 25.0 v

Concentrated aqueous solution of hydro- ,chloric acid (approx.'38% HCl) 48.0 Water 200.0

were heated together under reflux at the boiling temperature of the massfor 18 hours, after to the concentratedflltrate until a solid bezan The solution v to precipitate from the solution. was chilled to obtain a maximum yield of ,solid precipitate comprising (para-acetamido anilino) amino 1.2,4-triazoles. The product was removed from the solution by filtration and dried. The dried material had a melting point of about 200 C. with some indication of decomposition at this temperature.

The corresponding ortho and meta derivatives are prepared by using 135.2 parts of (oi-tho acetamido phenyl) bi'guanidehydrochloride o'rbiguanide Mal-'0',

(meta-acetamido phenyl) chloride instead of 135.2 parts of (para.- acetamido phenyl) biguanide hydrochloride.

I Example 2 'l-methyl (para-acetamido anilino) amino 1,2,4-triazoles' are prepared in essentially'the same manner as described under Example 1 with the exception that 23 parts of methyl hydrazine are used in place of 25 parts of hydrazine hydrate.

Example 3 l-phenyl (para-acetamido anilino) amino 1,2,4-triazoles are prepared in essentially the samemanner as described under Example 1 .with the exception that 54 parts of phenyl hydrazine are used instead of 25 parts of hydrazine hydrate. I p

, Example 4 Para-propanamido anilino) amino l.2,4 triazole are produced in essentially the same man- .In order that those skilled in the .art better may understand howthe'present invention may be carried into eflectgthe following examples are given by way of illustration and not by way oi limitation. All part fare by weight. ,Era'mple 1 This example illustrates the preparation of v (paraacetamido anilino) amino 1,2.4-triazoles,

which also may be named (para-acetylamino phenvlamino) amino 1.2, .-t1 'iazoles,. or '(paraacetylamino anilino). amino. 1,2,4-triazoles, or (para-acetamido .phenylamino') 1 amino 1,2,4 -triazoles.

ner as described under Example 1 withthe exception that 142.2 parts of (para-p'ropanamido 'phenyl) biguanide hydrochloride, which alsom'ay be named (para-propanoylamino phenyl) bigua-- nide of hydrochloride, are used in place of 135.2

. parts of (para-acetamid'ophenyl) biguanide hydrochloride.. r a

' Example 5 1 [(N-methyl para-acetamido) anilino] a' o 1,2,4-triazoles are prepared in essentiall the same manner as described under Example 1 with the exception that 142.2 parts of [(N'-methyl para-acetamido) phenyl] biguanide hydroohlo-f ride are used instead-oi 135.2 parts or (paraacetamido phenyl) I biguanide hydrochloride.

'More specific examples of compounds embraced by Formula I that may beproduced in accordance with the present, invention arelisted below: l-metl'rvl. (ortho-acetamido anilino) amino 1,2,4-

. triazoles l-methyl (meta-acetainldo anilino) amino 1,2,4-

t'riazoles l-phenyl (ortho-acetamido aniline) amino 1,2,4-

triazoles' I l-phenyl (meta-acetamide aniline) amine 1,2,4- triazoles (Orthe-propanamido aniline) amino 1,2,4-trlazoles, which may be represented by the termula XVII

(Meta-prepanamido aniline) amine 1,2,4-triazeles (Acetamido teluide) amine 1,2,4-triazoles, which may represented by the formula l-ethyl (acetamido aniline) amino 1,2,4-triazoles l-methyl (acetamido teluido) amino 1,2,4-triazoles l-phenyl (acetamide teluido) amino 1,2,4-triazeles (Propanamido toluide) amine 1,2,4-triazeles (Butanamido teluido) amino 1,2,4-triazeles (Isebutanamido -xylidino) amino 1,2,4-triazoles,

which may be represented by the formula XIX CH;

' (Prepenamido 'naphthylamino) amino 1,2,4-triazoles (Cyclopentanamido xenylamino) amino 1,2,4-triazeles (Benzamide aniline) amine 1,2,4-triazeles (Hexahydrobenzamido aniline) amino 1,2,4-triazeles (Benzam'ide toluido) amino 1,2,4-triazeles (Toluamido aniline) amine 1,2,4-triazoles (Toluamido teluide) amine 1,2,4-triazele (Acetamido ethyl aniline) amino 1,2,4-triazeles,

which may be represented by the formula 1 s I N-NH H:N[ II HC -e I L I I N NB-(fi-OH;

(Benzamido methyl naphthylamine) amino 1,2,4-

, triazoles (Dimethylbenzamido fluore aniline) amine 1,2,4-

triazoles, which may be represented by the for-- mula XXI

(Naphthamide aniline) amino 1,2.4Ftr1azo1es L-prepyl (acetamide toluide) amine 1,2,4-triazeles l-isebutyl (benzamide'aniline) amine 1,2,4-triazoles l-propenyl (benzamido aniline) amino-1,2,4-triazoles l-cyclopentyl (acetamido aniline) amino 1,2,4-

triazoles 1-pheny1 (methylbenzamido xylidine) 1,2,4-triazoles l-methyl [(N-methyl acetamide) aniline] amine 1,2,4-triaz oles, which may be represented by the formula amino l-benzyl ['(N-ethyl acetamide), aniline] amine [(N-isebutyl I benzamido) xenylamino] amine 1,2,4-triazoles [(N-phenyl benzami'do) aniline] amine 1,2,4 triazeles [(N-cyclepentyl acetamide) aniline] amino 1,2,4-

triazoles [(N-telyl acetamide) toluidol' amino 1,2,4-tri azeles l-methyl [(N-phenyl acetamide) aniline] amide 1,2;4-triazoles l-methyl [(N-methyl acetamido) naphthylamino] amino 1,2,4-triazeles l-phenyl [(N-phenyl acetamide) aniline] amine 1,2,4-tria2eles l-telyl (N-benzyl acetamido) propyl aniline] amine 1,2,4-triazoles l-ethyl [(N-phenethyl acetamido) toluido] amine 1,2,4-triaze1es l-allyl (acetamido aniline) amineLZA-triazeles It will be understood, of course, by those skilled in the art that in the'compound listed above the amine grouping may be attached to either the 3 or the 5 carbon atom of the triazele nucleus, the carbon atom which is not joined to an amine grouping being attached to the aeylaminoarylamino grouping; and, also, that the acylamine grouping may be attached to any of the reactive carbon atoms of the aromatic nucleus.

What I claim as new and desire to secure by Letters Patent of the United States is:

1. Chemical compounds corresponding to the general formula V where R represents a member of the class consisting of hydrogen.'and monovalent hydrocarbon radicals, R represents a monovalent, hydrocarbon where R represents a member of the class consisting of hydrogen and monovalent hydrocarbon radicals, R represents a monovalent hydrocarbon radical, and Z represents a divalent aromatic hydrocarbon radical.

3. Chemical compounds corresponding to the general formula where R represents a member of the class consisting of hydrogen and monovalent hydrocarbon I radicals, R represents a monovalent hydrocarbon radical, and Z represents a divalent aromatic hydrocarbon radical.

4. Chemical compounds corresponding to the general formula where R represents a monovalent hydrocarbon radical and Z represents a divalent aromatic hydrocarbon radical.

5. Chemical compounds corresponding to the general formula whcre R represents a monovalent hydrocarbon radical and Z represents aphenylene radical.

6. Chemical compounds corresponding to the general formula radicals, R represents a monovalent hydrocarbon where R represents an alkyl radical and Z represents 'a divalent aromatic hydrocarbon radical. '7. Chemical compounds corresponding to the general formula N where R represents an alkyl radical and Z represents a phenylene radical.

a. (Ortho-acetamido anilino) amino 1,2,4

triazoles. v

9. (Meta-acetamido anilino) amino 1,2,4- triazoles.

10. (Para-acetamido 'anilino) amino 1,2,4-

triazoles.

11. The method of preparing chemical compounds corresponding to 'the general formula where R represents a member of the class consisting of hydrogen and monovalent hydrocarbon radical, and Z represents a member of theclass consisting of divalent aromatic and nuclearly halogenated aromatic hydrocarbon radicals, said method comprising effecting reaction under heat between a hydrazine corresponding to the general formula where R has the meaning above given, and an ac'ylaminoaryl biguanide corresponding to the general formula NH NH o NHi- -NH -NHz-NR i-R' where R, R and Z have the meanings above given.

12. A method as in claim 11 wherein the reaction is carried out in the presence of an acid effective in binding the ammonia liberated during the reaction.

13. The method of preparing (para-acetamido anilino) amino 1,2,4-triazoles which comprises effecting reaction under heat between (paraacetamido phenyl) biguanide and hydrazine hydrate in the presence of an acid effective in binding the ammonia liberated during the reaction.

14. The method of preparing (para-acetamido anilino) amino 1,2,4-triazoles which comprises efi'ecting reaction under heat between (para- GAETANO F. DALELIO.

CERTIFICATE OF CORRECTION. Patent No. 2 7L 55. April 21;, 19L 5.

GAE'IANO F. D'ALELIO.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correcti on as follows: Page 1, first column, line 50, between formula III and formula IV insert the word "and"; and second column, line 50, for "actophenylene, actoxyphenylene" read -acetophenylene, acetoxyphenylene--; page 5, first column, lines 27 to 57 inclusive, for that portion of the formula reading "H 11" read -H2N--; and second column, line 57, after the syllable "nide" strike out "of"; page 14., second column, line 19, for "H 0" read -H C-; line 55, for

"amido" read -amino; and that the said Letters Patent should be read I with this correction therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 10th day of July, A. D. 1911.5.

Leslie Frazer (Seal) Acting Commissioner of Patents. 

